The Tick Saliva Peptide HIDfsin2 TLR4-Dependently Inhibits the Tick-Borne Severe Fever with Thrombocytopenia Syndrome Virus in Mouse Macrophages

SFTSV is a negative-strand RNA virus usually carried by the tick Haemaphysalis longicornis. HIDfsin2, the tick saliva peptide, activates the Toll-like receptor 4 (TLR4) by interacting with lipopolysaccharide (LPS), a ligand of TLR4, and then depolymerize LPS micelles into smaller particles. And activating TLR4 enhancing the activation of the nuclear factor kappa-B (NF-κB) and type I interferon (IFN-I) signaling pathways, which are downstream of TLR4.This reaction enhances the antiviral innate immunity of mouse macrophages. Therefore, HIDfsin2 enhance SFTSV replication in A549 and Huh7 cells (human cell lines) with low expression of TLR4. On the other hands, HIDfsin2 suppress SFTSV replication in mouse peritoneal macrophages (MPMs) with high expression of TLR4.
(RN)

The Mechanism of Genome Replication and Transcription in Bunyaviruses

The Bunyavirales order constitutes a diverse group of predominantly insect and rodent-borne viruses with a segmented, negative sense single-stranded RNA genome, which infect a wide range of vertebrate, invertebrate and plant hosts. Some bunyaviruses such as Lassa fever virus, Rift Valley fever virus, and Crimean Congo hemorrhagic fever virus are of serious public health concern as emphasized by their inclusion in the WHO R&D Blueprint list of priority diseases. While the viral large (L) polymerase protein containing the RNA-dependent RNA polymerase serves as the central factor of the viral replication cycle, and thus a suitable antiviral drug target, comparative knowledge about the structure and activities of this multifunctional protein across bunyaviruses has been limited and scattered in different literatures. Therefore, this study compiled the current information about the structures of the bunyavirus L proteins, and highlights the differences and commonalities in their genome replication and transcription processes as revealed by advanced cryogenic electron microscopy studies. In particular, insights into the 5' RNA hook coordination, distal duplex conformation, and 3' template RNA sequestration; viral genome replication priming, elongation, and termination; as well as viral transcription and cap-snatching mechanism were explained. In addition, the role of additional viral and host proteins, and comparison between bunyaviruses and the related influenza virus polymerase complexes were itemized to highlight sweeping questions for further research.
(BNU)

Structural and Biophysical Characterization of the Borna Disease Virus-1 Phosphoprotein

The mammalian orthobornavirus-1 commonly referred as Borna disease virus-1 (BoDV-1), is the prototype member of the Bornaviridae family associated with neurological impairments, encephalitis, and death in horses, cattle, and humans. Determining the structural organization of viral replication complexes and unraveilling the impact of infection on cellular homeostasis represent important challenges in virology.  As with other single stranded non-segmented RNA viruses, the BoDV-1 encodes a viral phosphoprotein (P) that binds both the viral polymerase (L) and nucleoprotein (N), and acts as a molecular chaperone required for the formation of functional replication/transcription complex. In this study, size-exclusion chromatography coupled with multi-angle laser X-ray scattering, circular dichroism, and differential scanning calorimetry were employed to determine the structural and biophysical organization of the BoDV-1 P. The protein was shown to adopts a stable tetrameric structure, with the regions outside the oligomerization domain being highly flexible. The long coiled helical structure splits into two parts at the midpoint of the oligomerization domain by a helix-breaking motif, which appears to be highly conserved across the members of the Bornaviridae. The stable tetramerization nature of the BoDV-1 P enables the viral protein to protect the viral RNA genome from host endonucleases, and effectively binds to the other components of the replicase complex.
(BNU)

Structure of Rift Valley Fever Virus RNA-Dependent RNA Polymerase

Rift valley fever virus (RVFV) is in the order Bunyavirales, family Phenuiviridae and genus Phlebovirus. It causes severe infections to both humans and animals (zoonotic) leading to significant economic losses. RVFV is a single stranded virus with three segments in its RNA genome namely large (L), medium (M) and small (S) segment. The L segment encodes for single polypeptide L protein which is an RNA dependent RNA polymerase (RdRp) while the M segment encodes for glycoprotein precursor and the S segment uses ambisence strategy to express NSs and nucleoprotein. The L protein is responsible for viral replication and transcription. Regarding treatment and prevention of infection, there is no specific drug therefore this study analyzed the function and structure of L protein using a cryo electron microscopy with resolution of 3.6 Å. This RdRp structure showed the mechanism of RNA synthesis and transcription. Their results showed that the RdRp is a promising drug target and can be explored further to develop antivirals for both humans and animals.
(BEC)

Selective Replication and Vertical Transmission of Ebola Virus in Experimentally Infected Angolan Free-Tailed Bats

In spite of the continuous sporadic Ebola virus (EBOV; Orthoebolavirus zairense) disease outbreaks with associated devastating public health, economic, and wildlife impacts for nearly five decades in Africa, a convincing natural reservoir host, as well as mechanisms of virus circulation in nature or spill over to humans are yet to be identified.  Bats have been reported as reservoirs of many zoonotic viruses including filoviruses, and experimental infections are often vital for understanding reservoir-pathogen interactions. Therefore, in this study, the permissiveness of Angolan free-tailed bats (AFBs) known to harbour filoviruses, to Ebola, Marburg, Taï Forest and Reston viruses was assessed. The experiment revealed that only the AFBs inoculated with EBOV showed marked disseminated viral replication, and shed infectious EBOV without displaying obvious clinical signs, as the other filoviruses failed to establish productive infections. In addition, the EBOV was shown to possess a unique placental-specific tissue tropism, and traversed the placental barriers to infect and persist in the AFBs foetal tissues resulting in distinct genetic signatures of adaptive evolution. Thus, AFBs reservoir competence, plausible transmission routes, and possible ancillary transmission mechanism that might be required to maintain EBOV within small reservoir populations have been described.
(BNU)

Tissue Distribution of Parrot Bornavirus 4 (PaBV-4) in Experimentally Infected Young and Adult Cockatiels (Nymphicus hollandicus)

Parrot bornavirus (PaBV) causes proventricular dilatation disease (PDD) of birds, causing predominantly nervous and gastrointestinal symptoms. PDD is fatal disease for birds. In order to detect the relevancy between the age of the animals at the time of infection and the PDD distribution in the body, we infected PaBV-4 to adults (group 1) 11 cockatiels and 11 juveniles (group 2) cockatiels by intravenous injection. In both cohorts, adult and juvenile PaBV-4-infected cockatiels, a widespread antigen and RNA tissue distribution was present. The results indicate that the virus spreads possibly not only via nerve tissue, but potentially also via endothelial cells, fibrocytes, and smooth muscle cells. Also, the histological lesions indicate that an age-related course of infection with more severe lesions in the CNS of adults but marked inflammation in gastrointestinal tract of juveniles despite lacking clinical signs. This contributes to understand the development of various clinical or non-clinical disease patterns and the development of carrier birds when infected as juveniles.

(RN)

Molecular Characterisation and Antibody Response to Bovine Respiratory Syncytial Virus in Vaccinated and Infected Cattle in Turkey

Bovine respiratory syncytial virus (BRSV) from the family Pneumoviridae causes severe respiratory disease in bovine leading to economic losses to the cattle industry. The genome of this virus has ten genes that encodes for eleven proteins. The eleven proteins are: glycoprotein (G), fusion protein (F), RNA polymerase (L), matrix protein (M), nucleoprotein (N), polymerase cofactors M2-1 and M2-2, phosphoprotein (P), small hydrophobic protein (SH), and the two non-structural proteins NS1 and NS2. Fever, coughing, decreased feed intake, increased breathing rate, oedema, and nasal discharge are the main clinical signs of this disease especially in calves. Vaccination is the major management component that aims at mitigating this respiratory disease. This study analyzed the immune status of vaccinated and non vaccinated cattle. Out of 162 sera samples 46% had antibodies to BRSV. Ten nasal swabs and 4 lung samples tested positive for BRSV RNA with RT-PCR. The results from this study show that seropositivity in vaccinated animals was statistically significant and that the rate of detection of BRSV-RNA in these animals was lower than in non-vaccinated animals
(BEC)

Multifunctionality of Matrix Protein in the Replication and Pathogenesis of Newcastle Disease Virus: A Review

Matrix (M) protein, is the most abundant structural protein of Newcastle disease virus (NDV) which occupies the inner layer of the virion envelope. Like in most known paramyxoviruses, the M protein has been well documented as the central organiser of viral morphogenesis, particularly, viral assembly and release. However, this review has compiled other known functions of the NDV M-protein including; impediment of host cell transcription, and regulation of viral RNA synthesis and transcription. In addition, the protein served as a conserved target in most molecular screening of NDV infections. Moreover, with its unique nuclear-cytoplasmic shuttling properties, NDV M-protein assists in viral protein synthesis; evasion of host immune responses; and enhances NDV replication, pathogenicity, and virulence.

(BNU)